This invention relates to a novel method for sterilizing fluids in a fluid sample including treatment of biological fluids for reintroduction into a human or other animal.
Sterilization of fluids is important in many processes including certain medical treatments. Because fluids have a certain defined volume it is hard to ensure that the entire sample is sterilized and penetration of sterilizing agents remains an ongoing challenge in sterilization processes.
Irradiation is one method by which some have tried to sterilize fluids. The amount of penetration of the irradiation is proportional to the energy level of the irradiation and also to the particulate content in the sample. For example, higher energy levels of UV light will penetrate a sample further but the thickness of the sample remains a constraint on the success of this technique, even when the sample is poured into a thin layer on a surface. At best there is sterilization around the periphery of the sample and this may not be sufficient to address the needs of the end user. Stirring of the sample is often not an adequate solution to this problem.
The thickness of the fluid layer is controlled, amongst other things, by the viscosity of the fluid, the surface tension of the fluid and the speed of flow of the fluid if it is moving. Many current methods involve sterilization of fluids as they move since the fluid is often being treated before being restored back into the original sample or directly back into the person or animal. Even methods in which the fluid moves along a surface or in tubing still must overcome the penetration hurdle in order to optimally sterilize the fluid. The depth of penetration will depend on the film thickness but generally penetration depth will be less than xc2xd the film thickness. Particulates in the sample will decrease penetration depth even more.
There are presently many examples of sterilization methods for fluids, in particular biological fluids, which incorporate ultraviolet irradiation in the sterilization process. U.S. Pat. No. 5,709,991 of Lin, et al. teaches methods for photodecontamination to inactive microorganisms in platelet preparations involving the use of psoralens. The method also includes step(s) for the removal of the psoralens after photodecontamination. The need for removal of psoralens after decontamination remains a constraint on the suitability of this approach for certain biological fluids.
Others have tried to reduce the volume of the sample by spreading the fluid out on a surface or using mesh whereby the fluid is stretched in the mesh but these methods do not permit a continuous flow system. These and other methods have been tried to increase the surface area which is exposed to the sterilization agent. UV irradiation has fallen into lesser use because of problems achieving full penetration of the UV light though the whole sample. The advantage of UV light is that it acts to disable the nucleic acids in microorganisms such as viruses and bacteria. Similarly certain cells can be disabled or killed by UV irradiation. White blood cells and any other cells containing nucleic acids will also be effectively made sterile when irradiated. Red blood cells however do not contain a nucleus or nucleic acids and will therefore not be similarly affected.
In accordance with an aspect of the present invention a method is provided for converting a volume of fluid into a continuous flow of thin and ultra thin portions of the fluid referred to as xe2x80x9cmembranesxe2x80x9d in this patent application. These membranes are so thin that irradiation, for example ultraviolet irradiation, will easily pan through the entire thickness of the membrane to effectively provide total sterilization in each fluid membrane portion. In accordance with another aspect, the method of the present invention can be used on clear fluids as well as fluids which contain particulates such as cells or other particles.
The principle of bolus flow using gas to create separate boli of fluid, or portions of a fluid sample, is coupled with a subsequent stretching of each fluid bolus into an extremely thin membrane which is then irradiated to achieve sterilization of that portion. The sterilized portions are later recombined and the complete fluid sample is effectively sterilized by this process.
The present invention has an advantage of providing a controlled system whereby fluid can be taken from one system, sterilized and then reintroduced into the original system after sterilization in a continuous flow system The thinness of the membranes advantageously allows for excellent and thorough sterilization of the fluid.
In accordance with an aspect of the present invention a method for sterilizing fluids is provided. The method comprises the steps of:
bolus dosing the fluid into a fluid flow system using a gas to create a continuous path of bolus volumes of the fluid interspersed with the gas;
moving the bolus volumes of fluid and gas in a continuous flow path through the system wherein the flow path gradually increases in width such that the fluid bolus is stretched into a fluid membrane, penetrable by irradiation;
sterilizing each stretched fluid membrane by exposing it to a sufficient dose of irradiation;
after sterilization, gradually narrowing the flow path width thereby increasing the thickness of each fluid membrane until it forms a droplet or is of suitable size to be collected; and
collecting the sterilized fluid droplets.
In accordance with a preferred embodiment of the present invention the fluid membrane is stretched to form a thin or ultra-thin film.
In accordance with another aspect of the method of the present invention the irradiation is ultraviolet irradiation (UVI) and/or the fluid flow system is comprised of UV penetrable tubing wherein the diameter of the tubing is gradually increased and then later decreased in accordance with the claimed method steps. In one embodiment the tubing may be catheter tubing.
In accordance with another aspect of the present invention a further step of debubbling is introduced prior to collecting the fluid droplet to prevent frothing of the fluid. In another embodiment the fluid is recondensed before collection. In yet another embodiment the fluid is taken directly from a patient, treated and introduced directly back into the patient.
In accordance with another aspect of the present invention, there are multiple cycles of the method steps to permit repeat sterilizations before collection.
Fluid samples which are treatable by the present invention include any biofluid including whole blood, plasma, serum, and vaccine sera.
In accordance with another aspect of the present invention a method is provided for inactivating one or more microorganisms in the preparation of a vaccine, the method comprising the steps of:
bolus dosing the fluid into a fluid flow system using a gas to create a continuous path of bolus volumes of the fluid interspersed with the gas;
moving the bolus volumes of fluid and gas in a continuous path through the system wherein the flow path gradually increases in width such that the fluid bolus is stretched into a fluid membrane, penetrable by irradiation;
sterilizing each fluid membrane as it moves through the system by exposing it to a sufficient dose of irradiation to inactivate the one or more microorganisms;
after sterilization, gradually narrowing the width of the flow path thereby increasing the width of each fluid membrane/bolus until it forms a droplet or is of suitable size to be collected; and
collecting the sterilized fluid droplet.